Are there associations between hip geometry and bone quality? An analysis on 3074 adults from a general population.

INTRODUCTION: Patients with reduced bone mineral density and altered hip geometry are susceptible for hip pathologies. Knowledge on associations between bone properties and hip geometric parameters might facilitate identification of patients at risk for hip pathologies. The aim of the present study was to identify associations of bone properties assessed by quantitative ultrasound (QUS) at the heel and hip geometric parameters like center-edge angle (CE), neck-shaft angle (NSA) and alpha angle. MATERIALS AND METHODS: Hip geometric parameters (CE, NSA and alpha angle) of 3074 participants from the population-based Study of Health in Pomerania were assessed on magnetic resonance imaging. QUS was performed on both calcanei providing broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness-index. Based on the stiffness-index the individual osteoporotic fracture risk (low, moderate or high) was determined. Associations between QUS-based and hip geometric parameters were calculated in linear regression models adjusted for age, sex, body height and weight. Interactions of QUS markers with age and sex on hip geometric parameters were tested. RESULTS: Significant inverse associations between BUA (ß = - 0.068), SOS (ß = - 0.024) as well as stiffness-index (ß = - 0.056) and CE were present, while fracture risk was positively associated with CE (ß for high = 1.28 and moderate = 2.54 vs. low fracture risk). Interactions between BUA and sex as well as between SOS and age were detected in the models for CE. Furthermore, there was an inverse relation between fracture risk and NSA that was restricted to the moderate risk (ß for moderate vs. low fracture risk = - 0.60). There were no significant associations between QUS parameters and alpha angle. CONCLUSIONS: In the general population, several associations between QUS-based bone properties or fracture risk and hip geometry are present. Less dysplastic hips had a lower stiffness-index and a higher fracture risk, whereas more valgus hips had a lower fracture risk.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

The Preventiometer - reliability of a cardiovascular multi-device measurement platform and its measurement agreement with a cohort study.

BACKGROUND: Multimedia multi-device measurement platforms may make the assessment of prevention-related medical variables with a focus on cardiovascular outcomes more attractive and time-efficient. The aim of the studies was to evaluate the reliability (Study 1) and the measurement agreement with a cohort study (Study 2) of selected measures of such a device, the Preventiometer. METHODS: In Study 1 (N = 75), we conducted repeated measurements in two Preventiometers for four examinations (blood pressure measurement, pulse oximetry, body fat measurement, and spirometry) to analyze their agreement and derive (retest-)reliability estimates. In Study 2 (N = 150), we compared somatometry, blood pressure, pulse oximetry, body fat, and spirometry measurements in the Preventiometer with corresponding measurements used in the population-based Study of Health in Pomerania (SHIP) to evaluate measurement agreement. RESULTS: Intraclass correlations coefficients (ICCs) ranged from .84 to .99 for all examinations in Study 1. Whereas bias was not an issue for most examinations in Study 2, limits of agreement for most examinations were very large compared to results of similar method comparison studies. CONCLUSION: We observed a high retest-reliability of the assessed clinical examinations in the Preventiometer. Some disagreements between Preventiometer and SHIP examinations can be attributed to procedural differences in the examinations. Methodological and technical improvements are recommended before using the Preventiometer in population-based research.

Reference values and influencing factors of the glenohumeral subluxation index: a study on 3004 participants.

BACKGROUND: The primary objective of this study was to examine the glenohumeral subluxation index (GHSI) in a large general population cohort and to define reference values. Glenohumeral subluxation is important in the development and prediction of pathological states of the shoulder joint and in total shoulder arthroplasty. Therefore, another objective was to examine the influence of age, sex, body mass index, and body height and weight on GHSI. METHODS: GHSI according to Walch was measured on bilateral magnetic resonance imaging of 3004 participants of the Study of Health in Pomerania (SHIP, aged 21-90 years). SHIP drew a sample of the adult general population of Pomerania (Northeastern Germany). Reference values for GHSI were assessed by quantile regression models. Associations of sex, age, and anthropometric markers with the GHSI were calculated by linear regression models. RESULTS: A reference range between 42% and 55% for men with a mean of 49% ± 4% was defined, while the upper reference limit for women was 1% higher (mean, 50% ± 4%). Age was inversely associated with the GHSI in males (P < 0.001), while no significant association in females was observed (P = .625). Body weight and body mass index were positively associated (P < .001) without effect modification by sex. Heavy mechanical oscillations on the upper extremity showed no significant association with GHSI (P = .268). CONCLUSION: The reference values for GHSI were expanded to a range of 42%-57% on magnetic resonance imaging. Several associations between GHSI and anthropometric properties are present. According to these associations, adjusted formulas are provided to enable individual, patient-specific diagnostics and therapy. Nevertheless, the clinical picture cannot be neglected.

Scale-up in twin-screw wet granulation: impact of formulation properties.

The focus of this study was to investigate the sensitivity of different drug formulations to differences in process parameters based on previously developed scale-up strategies. Three different formulations were used for scale-up experiments from a QbCon® 1 with a screw diameter of 16 mm and a throughput of 2 kg/h to a QbCon® 25 line with a screw diameter of 25 mm and a throughput of 25 kg/h. Two of those formulations were similar in their composition of excipients but had a different API added to the blend to investigate the effect of solubility of the API during twin-screw wet granulation, while the third formulation was based on a controlled release formulation with different excipients and a high fraction of HPMC. The L/S-ratio had to be set specifically for each formulation as depending on the binder and the overall composition the blends varied significantly in their response to water addition and their overall granulation behavior. Before milling there were large differences in granule size distributions based on scale (Earth Mover's Distance 140-1100 µm, higher values indicating low similarity) for all formulations. However, no major differences in granule properties (e.g. Earth Mover's Distance for GSDs: 23-88 µm) or tablet tensile strength (> 1.8 MPa at a compaction pressure of 200 MPa for all formulations with a coefficient of variation < 0.1, indicating high robustness for all formulations) were observed after milling, which allowed for a successful scale-up independent of the selected formulations.

Prospective, double-blind diagnostic multicentre study of confocal laser endomicroscopy for wheat sensitivity in patients with irritable bowel syndrome.

OBJECTIVE: A considerable proportion of patients with irritable bowel syndrome (IBS) may be wheat-sensitive and respond to a gluten-free diet (GFD) although they do not have coeliac disease. However, a diagnostic test for wheat sensitivity (WS) is missing. Our study evaluated the diagnostic accuracy (sensitivity and specificity) of confocal laser endomicroscopy (CLE) for the identification of WS as primary outcome. DESIGN: In this prospective, double-blind diagnostic study 147 non-coeliac patients fulfilling the Rome III criteria for IBS were tested by CLE for duodenal changes after wheat (index test), soy, yeast or milk exposure. Patients with IBS responding to 2 months of GFD were classified as having WS (reference test) using response criteria recommended by regulatory bodies for pharmaceutical trials of patients with IBS. After 2 months, CLE results were unblinded and patients were advised to exclude those food components that had led to a positive CLE reaction. The clinical response was assessed at follow-up after 6 and 12 months. RESULTS: Of 130 patients who completed the study per protocol, 74 (56.9%) responded to GFD and were classified as WS after 2 months, and 38 of these 74 patients were correctly identified by CLE (sensitivity 51.4%; 97.5% CI: 38.7% to 63.9%). A total of 38 of 56 patients without WS were correctly identified by CLE (specificity 67.9%; 97.5% CI: 52.9% to 79.9%). At 6 months follow-up, CLE correctly identified 49 of 59 food-sensitive patients (sensitivity 83.1%; 97.5% CI: 69.9% to 91.3%) but specificity was only 32% (97.5% CI: 15.7% to 54.3%). CONCLUSION: In light of the high proportion of patients with IBS responding to GFD, the diagnostic accuracy of CLE is too low to recommend widespread use of this invasive procedure. TRAIL REGISTRATION NUMBER: This study was registered as clinical trial in the German Registry for Clinical Studies (DRKS00010123).

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.

PURPOSE: The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC. METHODS: EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months. RESULTS: Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria "confirmed diagnosis of active UC within the last 6 months" (n = 2) and "immunosuppressive-naïve" (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed. CONCLUSION: Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.

Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

Variability of biomarkers used for the classification of metabolic syndrome: A repeated measurements study.

BACKGROUND AND AIMS: The definition of the metabolic syndrome consists of five components. The underlying measurements are subject to intra-individual variability. This repeated measurements study investigated the impact of intra-individual measurement variability on the stability of the diagnosis of metabolic syndrome over 12 months. METHODS AND RESULTS: Twenty-five employees of the University Medicine Greifswald aged 22-70 years were examined once a month over one year. Examinations included blood sampling and anthropometric and blood pressure measurements. Laboratory measurements included glucose, cholesterol (high-density lipoprotein [HDL], and low-density lipoprotein [LDL]), and triglycerides. The metabolic syndrome was defined according to the International Diabetes Federation modified for non-fasting blood samples. Variations in continuous metabolic markers were assessed using coefficients of variation (CV) and intra-class correlation coefficients (ICC). Overall eight participants (32%) were categorized at least once within 12 months as having a metabolic syndrome; in none of those metabolic syndrome was found consistently over the study follow-ups. The Cohen's Kappa for metabolic syndrome was 0.57. CV was highest for triglycerides (27.5%) followed by glucose (10.1%), LDL- (9.5%), and HDL-cholesterol (8.6%). ICC's were lowest for glucose (0.51), triglycerides (0.65), systolic (0.68), and diastolic blood pressure (0.69). CONCLUSION: We showed that the measurement of biomarkers defining the metabolic syndrome is a time-varying condition with implications for the concept of the metabolic syndrome. To account for this uncertainty in prevalence studies we propose to identify uncertain cases according to the current definition of the metabolic syndrome. For analysing associations we recommend to apply probabilistic sensitivity analyses.

Monitoring and management of chronic kidney disease in ambulatory care - analysis of clinical and claims data from a population-based study.

BACKGROUND: Although chronic kidney disease (CKD) is highly prevalent in the general population, little research has been conducted on CKD management in ambulatory care. Objective was to assess management and quality of care by evaluating CKD coding in ambulatory care, patient diagnosis awareness, frequency of monitoring and whether appropriate patients are referred to nephrology. METHODS: Clinical data from the population-based cohort Study of Health in Pomerania (SHIP-START) were matched with claims data of the Association of Statutory Health Insurance Physicians. Quality of care was evaluated according international and German recommendations. RESULTS: Data from 1778 participants (56% female, mean age 59 years) were analysed. 10% had eGFR < 60 ml/min/1.73m2 (mean age 74 years), 15% had albuminuria. 21% had CKD as defined by KDIGO. 20% of these were coded and 7% self-reported having CKD. Coding increased with GFR stage (G3a 20%, G3b 61%, G4 75%, G5 100%). Serum creatinine and urinary dip stick testing were billed in the majority of all participants regardless of renal function. Testing frequency partially surpassed recommendations. Nephrology consultation was billed in few cases with stage G3b-G4. CONCLUSION: CKD coding increased with stage and was performed reliably in stages ≥ G4, while CKD awareness was low. Adherence to monitoring and referral criteria varied, depending on the applicability of monitoring criteria. For assessing quality of care, consent on monitoring, patient education, referral criteria and coordination of care needs to be established, accounting for patient related factors, including age and comorbidity. TRIAL REGISTRATION: This study was prospectively registered as DRKS00009812 in the German Clinical Trials Register (DRKS).

Quality of life and sleep in individuals with irritable bowel syndrome according to different diagnostic criteria and inflammatory bowel diseases: A comparison using data from a population-based survey.

BACKGROUND: A proportion of irritable bowel syndrome (IBS) affected patients does not fulfil Rome criteria despite considerable impairment similarly to that in patients with organic gastrointestinal diseases.This investigation aims to examine differences regarding Mental (MQoL), Physical Quality of Life (PQoL), and sleep between IBS according to Rome III (IBS Rome), clinically defined IBS, inflammatory bowel diseases (IBD), and non-IBS/non-IBD individuals. METHODS: Data from SHIP-Trend (Study of Health in Pomerania, 2008-2012), a population-based cohort study in Germany, were used. RESULTS: Response was 50.1% (N = 4420). Prevalence was 3.5% for IBS Rome (95% confidence interval (CI): 3.0 - 4.1%, n = 148), 0.6% for clinically defined IBS (CI: 0.4 - 0.9%, n = 27), and 0.8% for IBD (CI: 0.6 - 1.1%, n = 34). Individuals with IBS Rome (4.54 (CI: -5.92; -3.17)) and clinically defined IBS (4.69 (CI: -7.82; -1.56)) had lower scores for MQoL compared to the non-IBS/non-IBD group. PQoL scores were lowered in IBS Rome (6.39 (CI: -7.89; -4.88)) and IBD (5.37 (CI: -8.51; -2.22)), but not in clinically defined IBS compared to the non-IBS/non-IBD group. IBS Rome was the only gastroenterological condition with higher odds of sleeping problems (odds ratio (OR) "falling asleep": 1.74; CI: 1.29; 2.36; OR "remaining asleep": 1.73; CI: 1.26; 2.38). CONCLUSIONS: IBS Rome is associated with reduced MQoL, PQoL, and sleep problems. Clinically defined IBS is associated only with reduced MQoL. Heterogeneity within IBS affected patients should be considered in clinical routine and screening for daily life impairment should be performed.

[Position paper on reporting of intestinal ultrasound findings in patients with inflammatory bowel disease]. / Positionspapier zur Befunderhebung von Darmultraschallbefunden bei chronisch entzündlichen Darmerkrankungen.

BACKGROUND: Intestinal ultrasound is increasingly used for primary diagnosis, detection of complications and monitoring of patients with Crohn's disease and ulcerative colitis. Standardization of reporting is relevant to ensure quality of the methodology and to improve communication between different specialties. The current manuscript describes the features required for optimized reporting of intestinal ultrasound findings in inflammatory bowel disease (IBD). METHODS: An expert consensus panel of gastroenterologists, radiologists, pathologists, paediatric gastroenterologists and surgeons conducted a systematic literature search. In a Delphi- process members of the Kompetenznetz Darmerkrankungen in collaboration with members of the German Society for Radiology (DRG) voted on relevant criteria for reporting of findings in intestinal ultrasound. Based on the voting results statements were agreed by expert consensus. RESULTS: Clinically relevant aspects of intestinal ultrasound (IUS) findings have been defined to optimize reporting and to standardize terminology. Minimal requirements for standardized reporting are suggested. The statements focus on description of disease activity as well as on complications of IBD. Attributes of intestinal inflammation are described and illustrated by exemplary images. CONCLUSION: The current manuscript provides practical recommendations on how to standardize documentation and reporting from intestinal ultrasound findings in patients with IBD.

Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting.

BACKGROUND: Periodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss. Comprehensive profiling of the metabolite content of the saliva can enable the identification of novel pathways associated with periodontitis and highlight non-invasive markers to facilitate time and cost-effective screening efforts for the presence of periodontitis and the prediction of tooth loss. METHODS: We first investigated cross-sectional associations of 13 oral health variables with saliva levels of 562 metabolites, measured by untargeted mass spectrometry among a sub-sample (n = 938) of the Study of Health in Pomerania (SHIP-2) using linear regression models adjusting for common confounders. We took forward any candidate metabolite associated with at least two oral variables, to test for an association with a 5-year tooth loss over and above baseline oral health status using negative binomial regression models. RESULTS: We identified 84 saliva metabolites that were associated with at least one oral variable cross-sectionally, for a subset of which we observed robust replication in an independent study. Out of 34 metabolites associated with more than two oral variables, baseline saliva levels of nine metabolites were positively associated with a 5-year tooth loss. Across all analyses, the metabolites 2-pyrrolidineacetic acid and butyrylputrescine were the most consistent candidate metabolites, likely reflecting oral dysbiosis. Other candidate metabolites likely reflected tissue destruction and cell proliferation. CONCLUSIONS: Untargeted metabolic profiling of saliva replicated metabolic signatures of periodontal status and revealed novel metabolites associated with periodontitis and future tooth loss.

Which factors are associated with bone marrow oedema suspicious of axial spondyloarthritis as detected by MRI in the sacroiliac joints and the spine in the general population?

OBJECTIVE: Identify factors associated with presence and extension of spinal and sacroiliac joints (SIJ)-MRI lesions suggestive of axial spondyloarthritis (axSpA) in a population-based cohort (Study of Health in Pomerania) aged <45 years. METHODS: Spinal (sagittal T1/T2) and SIJ (semicoronal STIR sequences) MRIs were evaluated by two trained blinded readers. The presence (yes/no) and extension (Berlin MRI Score) of bone marrow oedema (BME) were captured. Degenerative spinal lesions were excluded and discrepancies resolved by consensus. Cross-sectional associations between clinical factors and presence/extension of BME were analysed by logistic/negative binomial regression. Record linkage of claims data was applied to identify participants with axSpA. RESULTS: MRIs of 793 volunteers were evaluated. The presence of SIJ-BME (odds ratio) was strongly associated delivery during the last year (4.47, 1.49-13.41). For SIJ-BME extension, associations (incidence rate ratios, 95% CI) were found for delivery ((during last year) 4.52, 1.48-13.84), human leucocyte antigen (HLA)-B27+ (2.32, 1.30-4.14), body mass index (25-30 vs <25 kg/m²; 1.86 (1.19-2.89)) and back pain ((last 3 months) 1.55, 1.04-2.31), while for spinal BME, associations were found for age per decade (1.46, 1.13-1.90) and physically demanding work (1.46, 1.06-2.00). Record linkage was available for 694 (87.5%) participants and 9/694 (1.3%) had a record of axSpA (ICD M45.09). CONCLUSION: These population-based data support the hypothesis of mechanic strain contributing to BME in the general population aged <45 years and the role of HLA-B27+ as a severity rather than a susceptibility factor for SIJ-BME.

Shared Genetics of Multiple System Atrophy and Inflammatory Bowel Disease.

BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic etiology of this interaction remains unknown. We aimed to investigate genetic overlap between MSA and 7 autoimmune diseases and to identify shared genetic loci. METHODS: Genome-wide association study summary statistics of MSA and 7 autoimmune diseases were combined in cross-trait conjunctional false discovery rate analysis to explore overlapping genetic background. Expression of selected candidate genes was compared in transgenic MSA mice and wild-type mice. Genetic variability of candidate genes was further investigated using independent whole-exome genotyping data from large cohorts of MSA and autoimmune disease patients and healthy controls. RESULTS: We observed substantial polygenic overlap between MSA and inflammatory bowel disease and identified 3 shared genetic loci with leading variants upstream of the DENND1B and RSP04 genes, and in intron of the C7 gene. Further, the C7 gene showed significantly dysregulated expression in the degenerating midbrain of transgenic MSA mice compared with wild-type mice and had elevated burden of protein-coding variants in independent MSA and inflammatory bowel disease cohorts. CONCLUSION: Our study provides evidence of shared genetic etiology between MSA and inflammatory bowel disease with an important role of the C7 gene in both phenotypes, with the implication of immune and gut dysfunction in MSA pathophysiology. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fluorescence-encoded poly(methyl metharcylate) nanoparticles for a lateral flow assay detecting IgM autoantibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) belongs to the most often occurring autoimmune diseases in the world. For serological diagnosis, IgM auto-antibodies directed against the Fc portion of IgG referred to as rheumatoid factor are used as biomarkers. The autoantibody detection is usually done by ELISA. Such assays are reliable but are not suitable for point-of-care testing in contrast to lateral flow assays. Here, we report the development of a lateral flow assay based on carboxylated fluorescence-encoded poly(methyl methacrylate) nanoparticles. Poly(methyl methacrylate) is a non-toxic plastic with an excellent biocompatibility and high optical transparency which promises especially high sensitive fluorescence detection thereby leading to very sensitive assays. We could detect a positive signal in samples with a nephelometric reading down to 0.4 U/mL. By analyzing 30 sera of patients with a RA diagnosis and 34 sera of healthy test subjects we could confirm positive ELISA results in 72% of all cases and negative ELISA results in 97% of all cases.

Comparative Analysis of 3-Year Persistence With Vedolizumab Compared With Antibodies Against Tumor Necrosis Factor-Alpha in Patients With Inflammatory Bowel Disease in Germany: Retrospective Analysis of a Large Prescription Database.

AIMS: The goal of the study was to compare persistence with vedolizumab versus adalimumab, golimumab, and infliximab in biologics-naïve patients with inflammatory bowel disease treated in gastroenterological practices and outpatient clinics in Germany. METHODS: Patients aged 18 or older who had initiated a biological therapy (vedolizumab, infliximab, adalimumab, or golimumab) were included in the present study. Prescriptions between July 2014 and March 2017 of the respective biological drug emerging from gastroenterological practices or outpatient clinics in Germany were retrieved from the longitudinal prescription (LRx) database. Patients treated with vedolizumab were matched with patients treated with infliximab, adalimumab, or golimumab on the basis of age, gender, medication before biologic therapy, and index year. The primary outcome variable of the study was the rate of persistence with vedolizumab compared with antitumor necrosis factor biologics (infliximab, adalimumab, and golimumab) within 3 years of the first prescription in outpatient settings. RESULTS: Kaplan-Meier analysis was performed in 15,984 patients naïve to biologics revealing the statistically lower risk of discontinuation for vedolizumab compared with adalimumab, golimumab, or infliximab. In matched-pairs analyses, within 3 years after the first prescription, 39.5% of 2076 patients were persistent to vedolizumab compared with 33.5% of matched patients persistent to adalimumab (P<0.001). 37.6% of 716 patients were persistent to vedolizumab compared with 24.7% of matched patients persistent to golimumab (P<0.001). 35.7% of 2055 patients were persistent to vedolizumab compared with 30.2% of matched patients persistent to infliximab (P=0.119). Vedolizumab was associated with a significantly lower risk of therapy discontinuation compared with adalimumab [hazard ratio (HR)=0.86; 95% confidence interval (CI), 0.81-0.93] and golimumab (HR=0.60; 95% CI, 0.54-0.67), respectively; the vedolizumab risk of therapy discontinuation was numerically lower than infliximab but statistical significance was not achieved (HR=0.93; 95% CI, 0.85-1.02). CONCLUSION: In biologics-naïve IBD patients treated in outpatient settings in Germany, matched-pair analyses showed that vedolizumab was associated with significantly improved drug persistence compared with adalimumab or golimumab, whereas numerical improvement was shown in comparison with infliximab.

Facilitating harmonized data quality assessments. A data quality framework for observational health research data collections with software implementations in R.

BACKGROUND: No standards exist for the handling and reporting of data quality in health research. This work introduces a data quality framework for observational health research data collections with supporting software implementations to facilitate harmonized data quality assessments. METHODS: Developments were guided by the evaluation of an existing data quality framework and literature reviews. Functions for the computation of data quality indicators were written in R. The concept and implementations are illustrated based on data from the population-based Study of Health in Pomerania (SHIP). RESULTS: The data quality framework comprises 34 data quality indicators. These target four aspects of data quality: compliance with pre-specified structural and technical requirements (integrity); presence of data values (completeness); inadmissible or uncertain data values and contradictions (consistency); unexpected distributions and associations (accuracy). R functions calculate data quality metrics based on the provided study data and metadata and R Markdown reports are generated. Guidance on the concept and tools is available through a dedicated website. CONCLUSIONS: The presented data quality framework is the first of its kind for observational health research data collections that links a formal concept to implementations in R. The framework and tools facilitate harmonized data quality assessments in pursue of transparent and reproducible research. Application scenarios comprise data quality monitoring while a study is carried out as well as performing an initial data analysis before starting substantive scientific analyses but the developments are also of relevance beyond research.

Bidimensional structure and measurement equivalence of the Patient Health Questionnaire-9: sex-sensitive assessment of depressive symptoms in three representative German cohort studies.

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) has been proposed as a reliable and valid screening instrument for depressive symptoms with one latent factor. However, studies explicitly testing alternative model structures found support for a two-dimensional structure reflecting a somatic and a cognitive-affective dimension. We investigated the bidimensional structure of the PHQ-9, with a somatic (sleeping problems, fatigability, appetitive problems, and psychomotor retardation) and a cognitive-affective dimension (lack of interest, depressed mood, negative feelings about self, concentration problems, and suicidal ideation), and tested for sex- and regional-differences. METHODS: We have included data from the GEnder-Sensitive Analyses of mental health trajectories and implications for prevention: A multi-cohort consortium (GESA). Privacy-preserving analyses to provide information on the overall population and cohort-specific information and analyses of variance to compare depressive, somatic and cognitive-affective symptoms between sexes and cohorts were executed in DataSHIELD. In order to determine the dimensionality and measurement invariance of the PHQ-9 we tested three models (1 factor, 2 correlated factors, and bifactor) via confirmatory analyses and performed multi-group confirmatory factor analysis. RESULTS: Differences between sex and cohorts exist for PHQ-9 and for both of its dimensions. Women reported depressive symptoms in general as well as somatic and cognitive-affective symptoms more frequently. For all tested models an acceptable to excellent fit was found, consistently indicating a better model fit for the two-factor and bifactor model. Scalar measurement invariance was established between women and men, the three cohorts, and their interaction. CONCLUSIONS: The two facets of depression should be taken into account when using PHQ-9, while data also render support to a general factor. Somatic and cognitive-affective symptoms assessed by the PHQ-9 can be considered equivalent across women and men and between different German populations from different regions.

Pragmatic MDR: a metadata repository with bottom-up standardization of medical metadata through reuse.

BACKGROUND: The variety of medical documentation often leads to incompatible data elements that impede data integration between institutions. A common approach to standardize and distribute metadata definitions are ISO/IEC 11179 norm-compliant metadata repositories with top-down standardization. To the best of our knowledge, however, it is not yet common practice to reuse the content of publicly accessible metadata repositories for creation of case report forms or routine documentation. We suggest an alternative concept called pragmatic metadata repository, which enables a community-driven bottom-up approach for agreeing on data collection models. A pragmatic metadata repository collects real-world documentation and considers frequent metadata definitions as high quality with potential for reuse. METHODS: We implemented a pragmatic metadata repository proof of concept application and filled it with medical forms from the Portal of Medical Data Models. We applied this prototype in two use cases to demonstrate its capabilities for reusing metadata: first, integration into a study editor for the suggestion of data elements and, second, metadata synchronization between two institutions. Moreover, we evaluated the emergence of bottom-up standards in the prototype and two medical data managers assessed their quality for 24 medical concepts. RESULTS: The resulting prototype contained 466,569 unique metadata definitions. Integration into the study editor led to a reuse of 1836 items and item groups. During the metadata synchronization, semantic codes of 4608 data elements were transferred. Our evaluation revealed that for less complex medical concepts weak bottom-up standards could be established. However, more diverse disease-related concepts showed no convergence of data elements due to an enormous heterogeneity of metadata. The survey showed fair agreement (Kalpha = 0.50, 95% CI 0.43-0.56) for good item quality of bottom-up standards. CONCLUSIONS: We demonstrated the feasibility of the pragmatic metadata repository concept for medical documentation. Applications of the prototype in two use cases suggest that it facilitates the reuse of data elements. Our evaluation showed that bottom-up standardization based on a large collection of real-world metadata can yield useful results. The proposed concept shall not replace existing top-down approaches, rather it complements them by showing what is commonly used in the community to guide other researchers.